DESCRIPTION: Parasitic nematodes are among the world's most prevalent disease-causing organisms. Controlling them has largely depended on anti-parasite drugs that target the locomotory system, since locomotion is necessary for many parasitic nematodes to maintain their position within the host. Unfortunately, anthelmintic resistance has compromised the effectiveness of many antiparasite drugs, necessitating the refinement of these drugs and/or the search for new ones. The proposed research will use electrophysiological techniques to study the neuropharmacology of the primary inhibitory neurotransmitter system in nematodes, the GABA (gamma-aminobutyric acid) signaling system. In contrast to previous work that has focused on muscle, the aim of this research is to elucidate the GABA pharmacology of the nematode nervous system, specifically the motorneurons of the mOtornervous sytem which control locomotory behavior. This work will make use of the parasitic nematode Ascaris suum, a model system for nematode neurophysiology. The GABA signaling system consists of receptors and transporters. The pharmacology of GABA receptors will be studied with selective agonists and antagonists to characterize the receptors underlying GABA responses in the motornervous system. Likewise, the pharmacology of GABA transporters will be explored with substrates and inhibitors to characterize the transporters. Since the nervous system is ultimately responsible for control of behavior, any of these GABA-related drugs that compromise the normal function of the nervous system are likely to also disrupt locomotion. On the basis of these studies, the sole GABA-related anthelmintic currently in use (piperazine) may be refined and new anti-parasite drugs may be discovered.